Targeting Keap1 by miR-626 protects retinal pigment epithelium cells from oxidative injury by activating Nrf2 signaling.

Activation of the NF-E2-related factor 2 (Nrf2) cascade can offer significant protection against oxidative stress in retinal pigment epithelium (RPE) cells. Here, we identified a novel kelch-like ECH-associated protein 1 (Keap1)-targeting microRNA, microRNA-626 (miR-626) that activates Nrf2 signaling. In ARPE-19 cells and primary human RPE cells, ectopic overexpression of miR-626 targeting the 3'-UTR (3'-untranslated region) of Keap1 downregulated its expression, promoting Nrf2 protein stabilization and nuclear translocation, leading to expression of ARE-dependent genes (HO1, NOQ1 and GCLC).